The mechanism of action and regulation of contractile proteins will be investigated in this research project. The unusual 18O isotopic exchange properties of skeletal muscle myosin will be used to further our knowledge of the mechanism of the myosin ATPase. Particular emphasis will be placed on the influence of the supramolecular organization on the mechanism and the significance of this interaction for the correlation of events in ATP hydrolysis and the conformational changes in the proteins which produce tension and contraction. The other major area of research will be the investigation of the mechanism in smooth muscle and non-muscle myosin and the dynein ATPase of eucaryotic flagella. This will provide information about these systems themselves and will also allow an assessment of the generality of the mechanistic scheme which has been observed with skeletal muscle. Experiments are also proposed to develop kinetic and exchange criteria for analysis of actin-directed and myosin-directed control.